REVIEW Open Access

Anaphylactic Reactions to Oligosaccharides inRed Meat: a Syndrome in EvolutionHana Saleh1*, Scott Embry1, Andromeda Nauli1,2, Seif Atyia1 and Guha Krishnaswamy1

Abstract

Objective: While most allergic responses to food are directed against protein epitopes and occur within 30minutes of ingesting the allergen, recent studies suggest that delayed reactions may occur, sometimes mediatedby IgE antibodies directed against carbohydrate moieties. The objective of this review is to summarize the clinicalfeatures and management of delayed hypersensitivity reactions to mammalian meat mediated by IgE antibodies togalactose-alpha 1,3-galactose (alpha-gal), an oligosaccharide.

Methods: A PubMed search was conducted with MeSH terms: galactosyl-(1,3) galactose, oligosaccharides,cetuximab, allergy/hypersensitivity, and anaphylaxis. Reported cases with alpha-gal-mediated reactions werereviewed. This research study was approved by the Institutional Review Board of East Tennessee State University.

Results: Thirty-two cases of adults presenting with red-meat induced allergy thought to be related tooligosaccharides have been reported in the literature so far, making this a rare and evolving syndrome. Most ofthese patients demonstrated delayed reactions to beef, as was seen in the case reported by us in this manuscript.IgE specific to alpha-gal was identified in most patients with variable response to skin testing with beef and pork.Inhibition studies in some cases showed that the IgE antibodies to beef were directed towards alpha-gal in themeat rather than the protein. The patients often reported history of tick bites, the significance of which is unclearat present. Reactions to cetuximab, a monoclonal antibody, are mediated by a similar mechanism, with IgEantibodies directed against an alpha-gal moiety incorporated in the drug structure.

Conclusion: Alpha-gal is an oligosaccharide recently incriminated in delayed anaphylactic reactions to mammalianmeats such as to beef, pork, and lamb. It appears that anaphylactic reactions to the anti-cancer biological agent,cetuximab, may be linked mechanistically to the same process. More studies are required to understand theunderlying molecular basis for these delayed reactions in specific, and their broader implications for host defensein general.

Keywords: Galactosyl-(1,3) galactose, Oligosaccharides, Cetuximab, Anaphylaxis, Food allergy, Delayedhypersensitivity

IntroductionBeef Allergy and the New Evolving SyndromeFood allergy remains a well-recognized problem thataffects people of different ages and can alter their qual-ity of life [1,2]. Its prevalence and incidence seem to beincreasing over the past years [3-7] with more cases offood-induced anaphylaxis being reported [8-11]. Foodhypersensitivity reactions are usually mediated by IgE

antibodies against the incriminated food allergens suchas eggs, seafood, milk, tree nuts, peanuts, wheat, soy,and rarely beef (Additional file 1: Table S1) [8,10-13].The development of IgE-mediated reaction to a foodthat was well tolerated in the past sometimes constitutesa true diagnostic and therapeutic challenge to thepatient and the physician [14]. The prevalence of foodallergy has been increasing, with up to 4% of childrenhaving allergic reactions to one or more foods, of whichreactions to peanut, soy, wheat, and seafood are prob-ably most common [8,10-15]. While clinical tolerance tofood allergens occurs in many children, some such as

* Correspondence: saleh.hana@gmail.com1Department of Internal Medicine, Division of Allergy and ClinicalImmunology, Quillen College of Medicine, East Tennessee State University, P.O. Box 70622, Johnson City, Tennessee 37614-0622, USAFull list of author information is available at the end of the article

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© 2012 Saleh et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

peanut and shell fish are characterized by the tenacity ofthe sensitization and persistence of sensitivity into adult-hood [12,13,15-17].Among food allergies, hypersensitivity to red meat is

less common [18-22]. It was not adequately studieduntil recently, with a few reports emphasizing the prob-able cross reactivity between beef, cow’s milk, and othertypes of red meat [23-31]. Some of the reactions,referred to as “pork-cat syndrome”, involve cross-reac-tivity between cat epithelial allergens and pork [32-39].The presentations of allergic reactions to meat, asreported in the literature, are reviewed in Additional file2: Table S2. These include allergic reactions to meatprotein, oral allergy syndrome (food-pollen syndrome),the pork-cat syndrome as explained earlier, and someforms of exercise-induced anaphylaxis [18-41].It was assumed that reactions to mammalian meats

would be immediate, and due to IgE directed against spe-cific protein allergens such as bovine serum albumin(BSA) [22,27,42-46]. However, over the past few yearsinvestigators have described a new syndrome character-ized by delayed reactions to mammalian meat associatedwith IgE antibodies directed against oligosaccharides[14,47,48]. Chung et al. first reported on IgE antibodiesspecific to galactose-alpha 1,3-galactose (alpha-gal), anoligosaccharide present in non-primates [49,50], whenstudying allergic reactions in cancer patients treated withcetuximab [51]. Commins et al. later reported on the roleof oligosaccharides and IgE antibodies to alpha-gal inallergy to red meat [14,47,48]. This article will review 31cases of delayed beef reactions from around the world[18,48,52,53], along with one case from our clinic. Itsummarizes the current understanding of this rare, novel,and evolving syndrome.

Historical Perspectives in the Discovery of Alpha-gal-mediated AllergyAlpha-gal (Figure 1) is an oligosaccharide found in mam-malian cells of non-primates [49,50]. The alpha-gal epi-tope is present in beef, pork, lamb [14,47-49], and catdander [54,55], but is absent in chicken and fish [49].Beta-galactosyl alpha 1,3 galactosyl transferase, the enzymeneeded for formation of alpha-gal, is inactivated inhumans and higher mammals due to an evolutionary pro-cess. As a result, immunocompetent individuals may formIgG isotype antibodies to alpha-gal [49,56]. These antibo-dies contribute to immediate rejection of xenotransplantssuch as with “pig organs” in humans (recipients). At thesame time, the high immunogenicity of alpha-gal mayallow for the generation of anti-viral vaccines, as well astumor vaccines that also carry the alpha-gal epitope [49].Exposure to food allergens (including perhaps alpha-gal

in mammalian meat) results in the generation of IgGantibodies from B cells and hence development of

immune tolerance. In predisposed individuals, due topossible genetic/environmental factors (such as a fattydiet, or tick bites), exposure of antigen presenting cells toalpha-gal leads to Th2 activation and induction of inter-leukins, leading to IgE formation by B cells. This culmi-nates in mast cell activation, eosinophilia, and the fullgamut of IgE-mediated hypersensitivity reactions charac-terized by urticaria, angioedema, and progression to sys-temic anaphylaxis in some patients [8,57,58].

Cetuximab; Introduction, Infusion reactions, and Link toMeat AllergyCetuximab is a recombinant chimeric epidermal growthfactor monoclonal antibody approved for treatment ofmetastatic colorectal and head and neck cancer[51,59-61]. Initial studies on cetuximab started in 2000,when IMC-C225, was shown to inhibit the growth ofpancreatic cancer cells [62]. Further studies and clinicaltrials on this monoclonal antibody, later given the namecetuximab, were conducted [63-66]. It was shown thatcetuximab binds to tumor cells, and is able to activatenatural killer cells, eosinophils, and neutrophils to targetthem against these cancer cells [67]. In 2004, cetuximabwas approved for the treatment of colon cancer (http://www.fda.gov/NewsEvents/Newsroom/PressAnnounce-ments/2004/ucm108244.htm) [59], and subsequently fortreatment of squamous cell head and neck cancer in2006 (http://www.fda.gov/NewsEvents/Newsroom/Press-Announcements/2006/ucm108609.htm). Since 2002,cetuximab has induced severe hypersensitivity reactions[51,68-70] that have led physicians to further study thenature of these reactions, and determine the appropriatemanagement [71-73]. In 2007 and 2008, reports showedthat the infusion reactions were more prevalent in South-eastern United States [51,68] (Figure 2A). This distribu-tion is of interest, and may be related to other factors,including diet as well as exposure to the Lone Star Tick[74] (Figure 2B). In 2008, Chung et al. identified IgE anti-bodies to alpha-gal in patients who developed mild tosevere allergic reactions, including anaphylaxis, followingtreatment with cetuximab [51]. Then, in 2009, Comminset al. reported on a similar geographic distribution ofpatients presenting with delayed allergic reaction to redmeat, and studies were able to detect IgE to alpha-gal inthese patients as well [48]. More patients with this inter-esting syndrome were further studied in Europe in 2009and 2011 [18,52]. Figure 3 summarizes the chronologicalevents starting with the discovery of cetuximab, the aller-gic reactions reported, the role of alpha-gal in these reac-tions, and the link to red meat allergy.

The Cetuximab Hypersensitivity SyndromeReactions to biological agents (and most drugs) can beclassified as IgE and non-IgE mediated reactions, and

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can present in the form of skin, pulmonary, or cardiacmanifestations [77-79]. Non-IgE reactions may be sec-ondary to cytokine release and/or tumor lysis syndrome[80-84]. In the case of cetuximab, evidence suggests thatthese reactions are IgE mediated and represent trueanaphylaxis.As mentioned earlier, Chung et al. identified IgE anti-

bodies to alpha-gal in patients presenting with severeinfusion reactions to cetuximab [51]. In this series, theauthors reported on the presence of IgE antibodiesagainst cetuximab in sera from four groups of patients:76 patients treated with cetuximab in the South-EasternUnited States, 72 healthy control subjects in Tennessee,49 control subjects with cancer in California, 3 treatedwith cetuximab, and 341 control subjects in Boston. Theauthors show that 25/76 subjects treated with cetuximabin Tennessee had clinical hypersensitivity to the drug,and samples from 17 of those demonstrated IgE antibo-dies to cetuximab, compared to only 1/51 in thosepatients who did not have a hypersensitivity reaction.The IgE antibodies were also found in 15/72 controlsubjects in Tennessee and only in 3/49 samples inNorthern California and 2/341 control samples fromBoston. The studies showed that these IgE antibodiesare directed against the alpha-gal component of the Fabfragment of cetuximab heavy chain (Figure 4) [51,85]. Arecent study by van Bueren et al. [85] reported the pre-sence of alpha-gal epitopes in the Fc portion of severalmonoclonal antibodies including infliximab, basiliximab,palivizumab, panitumumab, and cetuximab. However,only cetuximab was found to contain alpha-gal in theFab region of the heavy chain, and interestingly, was the

only drug able to bind to IgE specific to alpha-gal (Fig-ure 4) [85]. IgE to alpha-gal failed to bind to the Fc por-tion of the drugs due to several factors [85]. This mightexplain the tolerance of some patients to panitumumabafter experiencing severe reactions to cetuximab [86-88].Each cetuximab molecule contains two alpha-gal epi-

topes that can cross-link the high affinity receptor forIgE (FcεRI) on mast cells [51]. IgE crosslinking of FcεRIleads to activation of mast cells and degranulation withrelease of hypersensitivity mediators including hista-mine, prostaglandins, leukotrienes, tryptase, and cyto-kines [57]. The possible mechanisms behind thecetuximab reactions are demonstrated in cartoon formatin Figure 4.

Clinical Presentation and Diagnosis of Alpha-gal-relatedMeat AllergyThe clinical presentation of alpha-gal-related red meatallergy is similar to other food allergies, but has manyunique characteristics (Additional file 3: Table S3).Upon presentation with suspected food allergy, historytaking remains the initial tool for diagnosis [12,18].Patients with beef allergy related to alpha-gal havesymptoms that are common to other food inducedhypersensitivity reactions including urticaria, dyspnea,hypotension, angioedema, or even full blown anaphylac-tic shock [18,48,52,53], but with the caveat that reac-tions occur hours after the ingestion of an incriminatedfood. This sometimes makes the diagnosis difficult. Adetailed history including type of ingested foods, time toonset of symptoms, the geographic area of residence aswell as history of tick bites, can help in achieving the

Figure 1 Structure of galactose-alpha 1,3-galactose (alpha-gal). Alpha-gal is an oligosaccharide found in mammalian cells of non-primates[49,50]. The alpha-gal epitope is present in beef, pork, lamb [14,47-49], and cat dander [54,55], and absent in chicken and fish [49]. Beta-galactosyl alpha 1,3 galactosyl transferase, the enzyme needed for formation of alpha-gal, is inactivated in humans and higher mammals [49,56].

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Figure 2 Areas in USA where IgE to alpha-gal is common and the associated tick. A: Map of United States of America with highlights onthe south-eastern region in which reactions to cetuximab [51], as well as seropositivity to alpha-gal in delayed red meat allergy [48], are mostprevalent. B: Lone star tick (Amblyomma americanum), most prevalent in southeast USA and linked to alpha-gal allergy [74-76]. Image used withpermission from Iowa State University Entomology department; Credit to John VanDyk.

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diagnosis. A patient presenting from the South-EasternUnited States with allergy to red meat occurring up to3-7 hours after ingestion, and with a history of tickbites, would be suggestive of alpha-gal allergy.In general, confirming the diagnosis of a specific food

allergy has many components. Although food challengesremain the “gold standard” for definitive diagnosis[12,13], most physicians would start with basic testsincluding skin prick test (SPT), intradermal testing, or

patch testing with the suspected allergen. In some caseswhere skin tests could not be performed, serum IgE anti-body quantification for the suspected allergen/s is safeand easy [12], but there is high number of false positiveresults, and the IgE level does not necessarily correlatewith the severity of the reaction [8,12]. The approach todelayed food reactions however has some caveats. A foodchallenge may be unnecessary if the history and serologi-cal tests are confirmatory, and may in fact be dangerous.

Figure 3 The events in the understanding of cetuximab and Alpha-gal-mediated hypersensitivity. With the use of cetuximab intreatment of head and neck cancer and colorectal carcinoma, multiple infusion reactions were reported. Chung el al. in 2008 were able toidentify IgE to alpha-gal directed to the Fab portion of cetuximab and was related to the allergic reactions. IgE to alpha-gal was later linked toallergic reactions to red meat in America and Europe. Information from references: [18,51,52,59-74].

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Food challenges are best conducted in research environ-ments and their role is yet to be defined in the delayedreactions to mammalian meats.In the USA, Commins et al. at University of Virginia

Health System are the leaders in studying delayed red

meat allergy [14,47,48]. They studied 24 patients withIgE to alpha-gal [48]: 4 initially presented with hyper-sensitivity to beef, 15 identified from a cohort study of243 patients, and 5 presenting from a clinic in Missouri.All 24 patients had delayed allergic reactions after

Figure 4 The possible mechanism behind cetuximab induced allergies. Cetuximab is a recombinant chimeric epidermal growth factormonoclonal antibody approved for treatment of metastatic colorectal and head and neck cancer [51,59-61]. Infusion reactions with cetuximabare linked to the presence of IgE antibodies directed against the alpha-gal component of the Fab fragment of cetuximab heavy chain [51,85].Each cetuximab molecule contains two alpha-gal epitopes that can cross-link the high affinity receptor for IgE (FcεRI) on mast cells [51] leadingto mast cell activation and release of hypersensitivity mediators [57].

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ingestion of red meat. Patients were between the ages of18 and 80 years, 14 males and 10 females, and present-ing from southeast United States. In addition to IgE toalpha-gal, total IgE levels, and IgE to beef were mea-sured in the studied cases. 22 out of 24 patients hadpositive (> 0.35 IU/ml) IgE to beef with variable totalIgE levels. Skin testing was performed on 18 patientsusing both commercial and fresh beef extracts, 13 ofwhich gave positive results. 10 patients had intradermaltesting to beef and all gave positive results. Althoughmore than 72% of patients had positive SPT to beef and100% of tested patients had positive intradermal tests tobeef, Commins reported that these reactions were notimpressive when compared to the IgE to beef, and theseverity of reactions they experienced [48]. Studiesshowed that fresh extracts of beef and pork containmore alpha-gal amounts than commercial extracts, andhence were able to produce better results [18,48]. Thisis no surprise as multiple reports showed that the aller-genicity of beef changes with the method of processingand heat exposure [26,89-92]. The source of meat andthe preparation of the extract used in SPT differbetween laboratories and even countries. This indeedcan attribute to the variability of results in each study.Almost 80% of the studied patients in Commins paperhad no further symptoms of hypersensitivity reactionsafter avoidance of red meat. The others had fewer mani-festations. Detailed information of the involved patientsand their laboratory results is outlined in Commins andPlatts-Mills original paper [48].Seven other patients studied in Europe presented with

delayed allergy to red meat, and had IgE levels positivefor alpha-gal and beef [18,52]. In France, investigationson two patients showed mild SPT reactions to raw beefand pork, but significant skin reaction when tested withcetuximab, even with low concentrations [18]. Nunez etal. in Spain also reported on 5 patients with IgE antibo-dies specific to alpha-gal, all presenting with severe redmeat allergy. All five patients tested positive for IgE tobeef, pork, lamb, and rabbit. SPT with raw beef andcetuximab were positive in all five as well [52]. Othercases with similar history and presentation to alpha-galallergy were reported, but to our knowledge testing foralpha-gal was not conducted [14,53]. Clinical presenta-tions of cases with alpha-gal allergy and variable diagnos-tic tests are summarized in Additional file 4: Table S4.A 48-year old male patient with delayed reaction to

beef presented to our clinic in East Tennessee. Heexperienced recurrent urticarial eruptions (Figure 5A)and dyspnea that occurred 5 to 7 hours after red meatingestion, including beef and pork. Interestingly, thepatient reported a history of tick bites 2 weeks prior tohis first reaction. Initial blood work showed negative IgElevels to beef and pork, but repeated testing of the same

sample was positive to beef. He also had very elevatedlevels of IgE specific to alpha-gal. Our patient nowavoids red meat products and has not experienced anyfurther reactions with food ingestion. Additional labora-tory data and information is summarized in Additionalfile 4: Table S4 and Figure 5B.

The Presumed Role of Tick BitesAlthough genetic factors may predispose an individualto develop an allergic reaction to beef, Commins pro-vided strong evidence that tick bites likely play animportant role in this development [48,74]. Bites fromthe tick species Amblyomma americanum (Lone Startick (Figure 2B)), commonly found in the south east andsouth central areas of the United States [75], seem toprecede the hypersensitivity to alpha-gal[74]. This phe-nomenon suggests a role in the sensitization process.The bite of the lone star tick is associated with the

development of STARI [76] (southern tick-associated rashillness) usually typified by a large “bulls eye” skin lesionand accompanied by fever, myalgia, and arthralgia. It isimportant to differentiate this illness from lime disease[76]. How instrumental tick bites are in alpha-gal sensiti-zation, and the mechanism by which this occurs is stillunclear.In a recent study, Commins and James reviewed three

patients with known IgE levels to alpha-gal, and documen-ted a significant elevation in these levels after exposure totick bites [74]. A strong correlation between antibodies toAmblyomma americanum and those to alpha-gal was pre-sent. Additionally, they screened several individuals andfound that most of those whose serum tested positive foralpha-gal, provided a history of tick bites, irrespective ofwhether they had developed meat reactions [74].In other areas of the world, history of tick bites (differ-

ent than Amblyomma americanum) is associated withdevelopment of meat-induced allergy [52,53]. In a studyby Van Nunen in Sydney Australia [53], almost allpatients (24/25) presenting with the red meat allergygave a history of tick bites. The suspected tick is Ixodesholocyclus [53], mainly distributed in southeastern Aus-tralia [93], and is associated with severe paralysis and car-diovascular problems [94-98]. In Spain 4 of 5 patientswith meat allergy expressed history of tick bites prior tothe reaction [52]. Although no documented proof of thetick species related to these reactions, the tick commonin that area in Spain (north-western) is Ixodes ricinus[52]. Cases with reported history of tick bites and the sus-pected tick are summarized in Additional file 4: Table S4.

Relationship to Dietary Fat and the Presumed Mechanismof DelayAnother interesting relationship between the areaswhere alpha-gal allergy is reported in the United States

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is the obesity rate. The recently reported obesity ratesfrom the Center of Disease Control and Prevention forTennessee, Arkansas, and North Carolina were higherthan those in California and Massachusetts, areas wherealpha-gal allergy is uncommon [51]. This raises thequestion of whether high-fat consumption in diet can bean additional reason for geographical alpha-gal IgEdistribution.The mechanism behind the delayed presentation of

symptoms after red meat ingestion in patients with IgEto alpha-gal is still undetermined. A possible explanationsuggested by Commins et al. proposes this delay to thetime needed for red meat to be digested and presentedto circulation [48]. Lipid and glycolipid complexes maymediate delayed absorption and presentation of alpha-gal to antigen presenting cells [14,48]. It only takesabout 2 hours for glucose to reach its maximum level inthe plasma after a meal. In contrast, it takes about 4-5hours for dietary triglycerides to reach their peak in cir-culation [99,100]. In the postprandial state, dietary tri-glycerides are packaged in the small intestine into very-low density lipoproteins (VLDLs) and chylomicrons, twoof the largest lipoprotein particles [101]. Due to theirlarge size, VLDLs (30-80 nm in diameter) and chylomi-crons (> 80 nm in diameter) are driven to enter thelymphatic circulation before being emptied into thevenous circulation via the subclavian vein. Soluble diet-ary nutrients, such as amino acids and glucose, directlyenter the venous circulation via the superior mesentericvein/hepatic portal vein. On the other hand, insolubledietary nutrients including long-chain triglycerides,

cholesterol, and lipid-soluble vitamins are packaged bythe small intestine into VLDLs and chylomicrons fortransport through the lymphatic circulation [102].Alpha-gal is known to be abundantly present on glyco-

lipids and glycoproteins of non-primate mammals,including the red meat from beef, pork, and lamb [49,50].Glycolipids and glycoproteins need to be digested in theintestinal lumen before they can be taken up by entero-cytes. These alpha-gal-containing digestion products arelikely lipid soluble and expected to be transported inVLDLs and/or chylomicrons [48]. The delay of both theallergic reaction and the peak of dietary triglycerides inthe circulation, suggests that the allergen from red meatis transported together with dietary triglycerides [48].Since lipoproteins are made out of a phospholipid mono-layer, the alpha-gal containing glycolipids may beinserted into the phospholipid monolayer with the carbo-hydrate group facing towards the exterior. The “exposed”orientation, rather than “buried”, should be optimal forinducing an allergic reaction. Studies should be aimedtowards determining the presence of alpha-gal in intest-inal lipoproteins. The presence of alpha-gal should onlybe detected in VLDL/chylomicron fractions from inges-tion of red meat from non-primate mammals, and notfrom other dietary sources, e.g., chicken and vegetarianmeals.

Food Anaphylaxis and Hypersensitivity ReactionManagementThe delay in appearance of symptoms related to alpha-gal allergy makes it difficult for patients and physicians

Figure 5 Urticarial eruptions (A) and laboratory data (B) in a patient with alpha-gal related red meat allergy. A 48 year-old patientpresented with recurrent urticarial eruptions and dyspnea 5 to 7 hours after red meat ingestion. Patient reported history of tick bites 2 weeksprior to his first reaction. Initial workup showed negative IgE to beef and pork. SPT to beef was not performed. Repeated testing was positive tobeef and alpha-gal. Patient avoids red meat products and symptoms are well controlled.

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to identify the trigger [14]. If such an event were tooccur, the patient would be advised to go to the nearesthospital or emergency room. Once the diagnosis is sus-pected on the basis of history and epidemiological set-ting, appropriate testing should be done to confirm thediagnosis. Following this, preventive measures includeavoidance of red meat and the use of injectable epi-nephrine [40,48,58,103]. Education and instruction onuse of injectable epinephrine is vital. Acute managementof patients presenting with anaphylaxis, including thoserelated to alpha-gal, is summarized in Additional file 5:Table S5.

ConclusionAlpha-gal allergy is a new and evolving syndromerelated to oligosaccharides, rather than protein, in redmeat. The IgE mediated response to alpha-gal tends tooccur several hours after antigen exposure. This uniquepresentation constitutes a challenge to both patients andphysicians, making detailed history very important ifsuspected. Reactions to cetuximab seem to be mediatedby an identical mechanism. More studies are requiredabout this unique syndrome, including an explanationfor the mechanism of delay in presentation and the pos-sible roles obesity and tick bites play in the predisposi-tion for the disorder.

Additional material

Additional file 1: Table 1. Common food allergens.

Additional file 2: Table 2. Meat Allergy Types and Features.

Additional file 3: Table 3. Diagnostic features of alpha-gal-related foodallergy.

Additional file 4: Table 4. Summary of reported cases with alpha-galallergy in USA and Europe.

Additional file 5: Table 5. Acute Management and Prevention ofAnaphylaxis*.

AbbreviationsAlpha-gal: Galactose-alpha 1,3-galactose; BSA: Bovine serum albumin; SPT:Skin-prick test; FEIA: Fluorescence enzyme immunoassay; VLDLs: Very-lowdensity lipoproteins; FDEIA: Food-dependent exercise-induced anaphylaxis;OSA: Ovine serum albumin.

Author details1Department of Internal Medicine, Division of Allergy and ClinicalImmunology, Quillen College of Medicine, East Tennessee State University, P.O. Box 70622, Johnson City, Tennessee 37614-0622, USA. 2Division of HealthSciences, East Tennessee State University, Johnson City, Tennessee, USA.

Authors’ ContributionsHS reviewed the literature, generated references, organized the manuscript,and illustrated the figures. SE assisted with manuscript review andcorrections. AN assisted in section involving mechanism of delay and role ofchylomicrons. SA assisted in section involving mechanism of delay and roleof chylomicrons. GK organized the manuscript, edited figures and tables,assisted in discussion, generated references, and participated in the editing

and final approval of the manuscript. All authors read and approved thefinal manuscript.

Competing InterestsThe authors declare that they have no competing interests.

Received: 14 November 2011 Accepted: 7 March 2012Published: 7 March 2012

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doi:10.1186/1476-7961-10-5Cite this article as: Saleh et al.: Anaphylactic Reactions toOligosaccharides in Red Meat: a Syndrome in Evolution. Clinical andMolecular Allergy 2012 10:5.

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